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Journal of Cerebral Blood Flow and Metabolism最新文献

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Cerebral microvascular physiology associated with white matter lesion burden differs by level of vascular risk in typically aging older adults. 与白质病变负担相关的脑微血管生理学因典型老龄化老年人的血管风险水平而异。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-20 DOI: 10.1177/0271678X241300394
Gabriele M Gassner, Nikou L Damestani, Natalie S Wheeler, Jan A Kufer, Shrikanth M Yadav, Sarah F Mellen, Katherine N Maina, David H Salat, Meher R Juttukonda

White matter lesions (WMLs) are prevalent with aging, and higher WML burden has been observed in older adults with vascular diseases. While the physiology underlying the formation of WMLs is not known, various risk factors are associated with high WML burden. Here, we investigated the relationship between vascular risk factors and microvascular physiology (i.e., oxygen supply and oxygen extraction fraction [OEF]) and their association with WML burden. Forty-one typically aging adults (60-80 years) were classified into high or low vascular risk based on common modifiable vascular risk factors (hypertension, diabetes, hyperlipidemia, and overweight). These groups were subdivided into high or low WML burden. Differences in microvascular physiology (oxygen supply and OEF) were then compared between and within groups. Overall, OEF was significantly higher in the high vascular risk group compared to the low vascular risk group (p < 0.01). In the low vascular risk subgroup, OEF was uniquely lower in the individuals with high WML versus low WML burden (p = 0.02), despite no differences in oxygen supply between these subgroups (p = 0.87). The coupling of impaired OEF with the absence of compensatory physiology, such as elevated oxygen supply, may represent an important mechanism underlying WML burden in individuals with low vascular risk factors.

白质病变(WMLs)随着年龄的增长而普遍存在,在患有血管疾病的老年人中观察到较高的 WML 负担。虽然 WMLs 形成的生理学原理尚不清楚,但各种风险因素都与高 WML 负担有关。在此,我们研究了血管风险因素和微血管生理(即供氧量和氧提取率 [OEF])之间的关系及其与 WML 负荷的关联。根据常见的可改变的血管风险因素(高血压、糖尿病、高脂血症和超重),我们将 41 名典型的老年人(60-80 岁)分为血管风险高和低两组。这些组别又被细分为高或低 WML 负担组。然后比较组间和组内的微血管生理差异(供氧和 OEF)。总体而言,高血管风险组的 OEF 明显高于低血管风险组(p
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引用次数: 0
Associations of life-course cardiovascular risk factors with late-life cerebral haemodynamics. 终生心血管风险因素与晚年脑血流动力学的关联。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-17 DOI: 10.1177/0271678X241301261
Mathijs Bj Dijsselhof, Jorina Holtrop, Sarah-Naomi James, Carole H Sudre, Kirsty Lu, Luigi Lorenzini, Lyduine E Collij, Catherine J Scott, Emily N Manning, David L Thomas, Marcus Richards, Alun D Hughes, David M Cash, Frederik Barkhof, Jonathan M Schott, Jan Petr, Henk Jmm Mutsaerts

While the associations of mid-life cardiovascular risk factors with late-life white matter lesions (WMH) and cognitive decline have been established, the role of cerebral haemodynamics is unclear. We investigated the relation of late-life (69-71 years) arterial spin labelling (ASL) MRI-derived cerebral blood flow (CBF) with life-course cardiovascular risk factors (36-71 years) and late-life white matter hyperintensity (WMH) load in 282 cognitively healthy participants (52.8% female). Late-life (69-71 years) high systolic (B = -0.15) and diastolic (B = -0.25) blood pressure, and mean arterial pressure (B = -0.25) were associated with low grey matter (GM) CBF (p < 0.03), and white matter CBF (B = -0.25; B = -0.15; B = -0.13, p < 0.03, respectively). The association between systolic blood pressure and GM CBF differed between sexes (male/female B = -0.15/0.02, p = 0.04). No associations were found with early- or mid-life cardiovascular risk factors. Furthermore, WMHs were associated with cerebral haemodynamics but not cardiovascular risk factors. These findings suggest that cerebral blood flow autoregulation is able to maintain stable global cerebral haemodynamics until later in life. Future studies are encouraged to investigate why cardiovascular risk factors have differential effects on haemodynamics and WMH, and their implications for cognitive decline.

虽然中年心血管风险因素与晚年白质病变(WMH)和认知能力下降的关系已经确定,但脑血流动力学的作用还不清楚。我们研究了 282 名认知能力健康的参与者(52.8% 为女性)的晚年(69-71 岁)动脉自旋标记(ASL)核磁共振成像衍生脑血流(CBF)与生命历程中的心血管风险因素(36-71 岁)和晚年白质高密度(WMH)负荷的关系。晚年(69-71 岁)高收缩压(B = -0.15)和舒张压(B = -0.25)以及平均动脉压(B = -0.25)与低灰质(GM)CBF 相关(P<0.05)。
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引用次数: 0
Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease. 中枢神经系统疾病模型中线粒体转移的分子和细胞机制。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-14 DOI: 10.1177/0271678X241300223
Takafumi Nakano, Keiichi Irie, Koichi Matsuo, Kenichi Mishima, Yoshihiko Nakamura

In the central nervous system (CNS), neuronal function and dysfunction are critically dependent on mitochondrial integrity and activity. In damaged or diseased brains, mitochondrial dysfunction reduces adenosine triphosphate (ATP) levels and impairs ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial capacity to generate ATP may be fundamental in restoring neuronal function. Recent studies in animals and humans have demonstrated that endogenous mitochondria may be released into the extracellular environment and transported or exchanged between cells in the CNS. Under pathological conditions in the CNS, intercellular mitochondria transfer contributes to new classes of signaling and multifunctional cellular activities, thereby triggering deleterious effects or promoting beneficial responses. Therefore, to take full advantage of the beneficial effects of mitochondria, it may be useful to transplant healthy and viable mitochondria into damaged tissues. In this review, we describe recent findings on the mechanisms of mitochondria transfer and provide an overview of experimental methodologies, including tissue sourcing, mitochondrial isolation, storage, and modification, aimed at optimizing mitochondria transplantation therapy for CNS disorders. Additionally, we examine the clinical relevance and potential strategies for the therapeutic application of mitochondria transplantation.

在中枢神经系统(CNS)中,神经元的功能和功能障碍严重依赖于线粒体的完整性和活性。在受损或患病的大脑中,线粒体功能障碍会降低三磷酸腺苷(ATP)水平,并损害依赖 ATP 的神经发射和神经递质动态。恢复线粒体产生 ATP 的能力可能是恢复神经元功能的基础。最近对动物和人类的研究表明,内源性线粒体可释放到细胞外环境中,并在中枢神经系统的细胞间运输或交换。在中枢神经系统病理条件下,细胞间线粒体转运有助于产生新的信号和多功能细胞活动,从而引发有害影响或促进有益反应。因此,为了充分利用线粒体的有益作用,将健康、有活力的线粒体移植到受损组织中可能是有益的。在这篇综述中,我们介绍了线粒体转移机制的最新发现,并概述了旨在优化中枢神经系统疾病线粒体移植疗法的实验方法,包括组织来源、线粒体分离、储存和修饰。此外,我们还探讨了线粒体移植的临床意义和潜在的治疗应用策略。
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引用次数: 0
A dangerous liaison: Spreading depolarization and tissue acidification in cerebral ischemia. 危险的联系脑缺血时蔓延性去极化和组织酸化。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-13 DOI: 10.1177/0271678X241289756
Eszter Farkas, Christine R Rose

Brain pH is precisely regulated, and pH transients associated with activity are rapidly restored under physiological conditions. During ischemia, the brain's ability to buffer pH changes is rapidly depleted. Tissue oxygen deprivation causes a shift from aerobic to anaerobic metabolism and the accumulation of lactic acid and protons. Although the degree of tissue acidosis resulting from ischemia depends on the severity of the ischemia, spreading depolarization (SD) events emerge as central elements to determining ischemic tissue acidosis. A marked decrease in tissue pH during cerebral ischemia may exacerbate neuronal injury, which has become known as acidotoxicity, in analogy to excitotoxicity. The cellular pathways underlying acidotoxicity have recently been described in increasing detail. The molecular structure of acid or base carriers and acidosis-activated ion channels, the precise (dys)homeostatic conditions under which they are activated, and their possible role in severe ischemia have been addressed. The expanded understanding of acidotoxic mechanisms now provides an opportunity to reevaluate the contexts that lead to acidotoxic injury. Here, we review the specific cellular pathways of acidotoxicity and demonstrate that SD plays a central role in activating the molecular machinery leading to acid-induced damage. We propose that SD is a key contributor to acidotoxic injury in cerebral ischemia.

大脑 pH 值受到精确调节,在生理条件下,与活动相关的 pH 值瞬态会迅速恢复。缺血时,大脑缓冲 pH 值变化的能力会迅速耗尽。组织缺氧会导致有氧代谢转变为无氧代谢,并造成乳酸和质子的积累。虽然缺血导致的组织酸中毒程度取决于缺血的严重程度,但扩散性去极化(SD)事件是决定缺血组织酸中毒的核心要素。脑缺血期间组织 pH 值的显著降低可能会加剧神经元损伤,与兴奋毒性类似,这种损伤被称为酸毒性。酸中毒的细胞通路最近得到了越来越详细的描述。研究人员探讨了酸或碱载体和酸中毒激活离子通道的分子结构、它们被激活的精确(失调)平衡条件以及它们在严重缺血中可能发挥的作用。对酸中毒机制的进一步了解为重新评估导致酸中毒损伤的环境提供了机会。在这里,我们回顾了酸毒性的特定细胞途径,并证明 SD 在激活导致酸诱导损伤的分子机制中发挥着核心作用。我们认为,SD 是导致脑缺血酸毒性损伤的关键因素。
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引用次数: 0
Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence. 大血管血流量和微血管脑血管反应性在青春期具有区域耦合性。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-13 DOI: 10.1177/0271678X241298588
Kristina M Zvolanek, Jackson E Moore, Kelly Jarvis, Sarah J Moum, Molly G Bright

Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n = 12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity (CVR) in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.

在青少年群体中,脑血管成像评估尤其具有挑战性,因为并非所有的成像模式都适合青少年,而且大脑的快速成熟会改变宏观和微观血管尺度的血流动力学。我们以健康青少年(n = 12,8-25 岁)为初步样本,研究了双侧大脑前、中、后动脉的 4D 流磁共振成像衍生血流速度和血流量与相关血管区域的 BOLD 脑血管反应性(CVR)之间的关系。根据假设,大动脉中较高的血流速度与下游区域对血管扩张刺激的较早反应(脑血管反应性延迟)有关。通过这些动脉的较高血流量与相关区域对血管扩张性刺激的较大 BOLD 反应(脑血管反应性振幅)有关。这些趋势在成人莫亚莫亚病的病例研究中是一致的。在我们的小型青少年队列中,速度/延迟和流量/CVR 的大血管-微血管关系随着年龄的增长而变化,但其潜在机制尚不清楚。我们的研究强调,需要更好地描述人类大脑发育的这一关键阶段,因为此时脑血管血流动力学正在发生变化,而标准成像方法对这些过程的洞察力有限。我们为未来的病理学比较提供了重要的标准数据,结合宏观和微观血管评估可更好地帮助我们预防、分层和治疗脑血管疾病。
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引用次数: 0
Differential vulnerability among cell types in the neurovascular unit: Description and mechanisms. 神经血管单元中不同类型细胞之间的脆弱性差异:描述与机制
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-09 DOI: 10.1177/0271678X241299960
Allison Brookshier, Patrick Lyden

Currently, successful preclinical cerebroprotective agents fail to translate effectively into clinical practice suggesting the need for a comprehensive evaluation of all aspects of brain function. Selective vulnerability refers to the specific regional response of the brain following global ischemia, with observed patterns of vulnerability attributed to the distribution of neuronal subtypes and the functions of respective brain regions. Conversely, the concept of differential vulnerability pertains to the cell-type-specific reactions to cerebral ischemia, dictated by the biological characteristics of individual cells. This review aims to explore these vulnerability hypotheses and elucidate potential underlying cellular mechanisms.

目前,成功的临床前脑保护剂未能有效地应用于临床实践,这表明需要对大脑功能的各个方面进行全面评估。选择性易损性指的是大脑缺血后特定区域的反应,观察到的易损性模式可归因于神经元亚型的分布和各自脑区的功能。相反,差异易损性的概念涉及细胞类型对脑缺血的特异性反应,这是由单个细胞的生物特性决定的。本综述旨在探讨这些易损性假说,并阐明潜在的潜在细胞机制。
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引用次数: 0
Sensitivity assessment of QSM+qBOLD (or QQ) in detecting elevated oxygen extraction fraction (OEF) in physiological change. 对 QSM+qBOLD(或 QQ)检测生理变化中氧萃取分数(OEF)升高的灵敏度进行评估。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-05 DOI: 10.1177/0271678X241298584
Praveena Elanghovan, Thanh Nguyen, Pascal Spincemaille, Ajay Gupta, Yi Wang, Junghun Cho

The study investigated the sensitivity of a novel MRI-based OEF mapping, quantitative susceptibility mapping plus quantitative blood oxygen level-dependent imaging (QSM+qBOLD or QQ), to physiological changes, particularly increased oxygen extraction fraction (OEF) by using hyperventilation as a vasoconstrictive stimulus. While QQ's sensitivity to decreased OEF during hypercapnia has been demonstrated, its sensitivity to increased OEF levels, crucial for cerebrovascular disorders like vascular dementia and Parkinson's disease, remains unexplored. In comparison with a previous QSM-based OEF, we evaluated QQ's sensitivity to high OEF values. MRI data were obtained from 11 healthy subjects during resting state (RS) and hyperventilation state (HV) using a 3 T MRI with a three-dimensional multi-echo gradient echo sequence (mGRE) and arterial spin labeling (ASL). Region of interest (ROI) analysis and paired t-tests were used to compare OEF, CMRO2 and CBF between QQ and QSM. Similar to QSM, QQ showed higher OEF during HV compared to RS: in cortical gray matter, QQ-OEF and QSM-OEF was 36.4±4.7% and 35.3±12.5% at RS and 45.0±11.6% and 45.0±14.8% in HV, respectively. These findings demonstrate QQ's ability to detect physiological changes and suggest its potential in studying brain metabolism in neurological disorders.

这项研究通过使用过度通气作为血管收缩刺激,研究了基于磁共振成像的新型OEF图谱--定量易感图谱加定量血氧水平依赖性成像(QSM+qBOLD或QQ)--对生理变化的敏感性,特别是对氧提取分数(OEF)增加的敏感性。虽然 QQ 对高碳酸血症时 OEF 降低的敏感性已得到证实,但其对 OEF 水平升高的敏感性(这对血管性痴呆和帕金森病等脑血管疾病至关重要)仍有待探索。与之前基于 QSM 的 OEF 相比,我们评估了 QQ 对高 OEF 值的敏感性。我们使用三维多回波梯度回波序列(mGRE)和动脉自旋标记(ASL)的 3 T MRI 获取了 11 名健康受试者在静息状态(RS)和过度换气状态(HV)下的 MRI 数据。采用感兴趣区(ROI)分析和配对 t 检验比较了 QQ 和 QSM 的 OEF、CMRO2 和 CBF。与 QSM 相似,与 RS 相比,QQ 在 HV 期间显示出更高的 OEF:在皮层灰质中,QQ-OEF 和 QSM-OEF 在 RS 中分别为 36.4 ± 4.7% 和 35.3 ± 12.5%,在 HV 中分别为 45.0 ± 11.6% 和 45.0 ± 14.8%。这些发现证明了 QQ 检测生理变化的能力,并表明其在研究神经系统疾病的脑代谢方面具有潜力。
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引用次数: 0
Impact of intracranial hypertension and cerebral perfusion pressure on spreading depolarization. 颅内高压和脑灌注压对展期去极化的影响
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-05 DOI: 10.1177/0271678X241296799
Takuma Nishimoto, Fumiaki Oka, Takao Inoue, Hiroshi Moriyama, Reo Kawano, Michiyasu Suzuki, David Y Chung, Cenk Ayata, Hideyuki Ishihara

Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO2), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration.

脑卒中和脑外伤后会出现扩展性去极化(SD),并可能导致继发性脑损伤。这些疾病通常伴有颅内高压,但人们对颅内压(ICP)对 SD 的影响知之甚少。在此,我们研究了ICP升高对大鼠血液动力学和新陈代谢对SD反应的影响。在不同的 ICP 和脑灌注压 (CPP) 下触发 SD。记录区域脑血流量(rCBF)、脑组织氧分压(PbtO2)、脑细胞外葡萄糖和乳酸浓度。荧光玉染色用于量化大脑皮层的神经元损伤。在高 ICP(50 mmHg)和低 CPP(30 mmHg)条件下,rCBF 和 PbtO2 呈单相降低,而正常条件下则呈单相升高。两个半球的神经元死亡都增加了,但触发 SD 的一侧增加得更多。在高 ICP(50 mmHg)和正常 CPP(70 mmHg)条件下,SD 期间的 CBF 和新陈代谢与基线没有差异,即使在诱发 SD 的一侧,神经元死亡也没有增加。这些数据表明,即使当 ICP 高达 50 mmHg 时,将 CPP 保持在 70 mmHg,也能在 SD 事件期间保持正常的血流和新陈代谢,并防止神经元变性。
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引用次数: 0
Retinal microvascular phenotypes can track small vessel disease burden and CPAP treatment effectiveness in obstructive sleep apnoea. 视网膜微血管表型可追踪阻塞性睡眠呼吸暂停患者的小血管疾病负担和 CPAP 治疗效果。
IF 5.4 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-02 DOI: 10.1177/0271678X241291958
Ylenia Giarratano, Elizabeth A Hill, Charlene Hamid, Stewart Wiseman, Calum Gray, Francesca M Chappell, Roberto Duarte Coello, Maria C Valdés-Hernández, Lucia Ballerini, Michael S Stringer, Michael J Thrippleton, Daniela Jaime Garcia, Xiaodi Liu, William Hewins, Yajun Cheng, Sandra E Black, Andrew Lim, Rosa Sommer, Joel Ramirez, Bradley J MacIntosh, Rosalind Brown, Fergus Doubal, Tom MacGillivray, Joanna M Wardlaw, Renata Riha, Miguel O Bernabeu

Optical coherence tomography angiography (OCT-A) retinal imaging enables in vivo visualization of the retinal microvasculature that is developmentally related to the brain and can offer insight on cerebrovascular health. We investigated retinal phenotypes and neuroimaging markers of small vessel disease (SVD) in individuals with obstructive sleep apnoea (OSA). We enrolled 44 participants (mean age 50.1 ± SD 9.1 years) and performed OCT-A imaging before and after continuous positive airway pressure (CPAP) therapy. Pre-treatment analyses using a generalized estimating equations model adjusted for relevant covariates, revealed perivascular spaces (PVS) volume in basal ganglia associated with greater foveal vessel density (fVD) (p-value < 0.001), and smaller foveal avascular zone area (p-value = 0.01), whereas PVS count in centrum semiovale associated with lower retinal vessel radius (p-value = 0.02) and higher vessel tortuosity (p-value = 0.01). A reduction in retinal vessel radius was also observed with increased OSA severity (p-value = 0.05). Post-treatment analyses showed greater CPAP usage was associated with a decrease in fVD (p-value = 0.02), and increased retinal vessel radius (p-value = 0.01). The findings demonstrate for the first time the potential use of OCT-A to monitor CPAP treatment and its possible impact on both retinal and brain vascular health.

光学相干断层血管成像(OCT-A)视网膜成像技术能够在体内观察到与大脑发育相关的视网膜微血管,并能深入了解脑血管的健康状况。我们研究了阻塞性睡眠呼吸暂停(OSA)患者的视网膜表型和小血管疾病(SVD)的神经影像标记。我们招募了 44 名参与者(平均年龄 50.1 ± SD 9.1 岁),并在持续气道正压(CPAP)治疗前后进行了 OCT-A 成像。使用广义估计方程模型进行治疗前分析,并对相关协变量进行调整,结果显示基底节的血管周围空间(PVS)体积与更大的眼窝血管密度(fVD)相关(p值为0.05)。
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引用次数: 0
Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy. 核磁共振成像上的白质微结构损伤与荷兰型脑淀粉样血管病的病情严重程度有关。
IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2024-11-01 Epub Date: 2024-06-17 DOI: 10.1177/0271678X241261771
Ingeborg Rasing, Naomi Vlegels, Manon R Schipper, Sabine Voigt, Emma A Koemans, Kanishk Kaushik, Rosemarie van Dort, Thijs W van Harten, Alberto De Luca, Ellis S van Etten, Erik W van Zwet, Mark A van Buchem, Huub Am Middelkoop, Geert Jan Biessels, Gisela M Terwindt, Matthias Jp van Osch, Marianne Aa van Walderveen, Marieke Jh Wermer

Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77-9.50]mm2/s × 10-4) compared with presymptomatic mutation-carriers (2.62 [1.96-3.43]mm2/s × 10-4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16-0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08-0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22-0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13-0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = -0.42 [-0.69-0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.

骨架化平均弥散度峰值宽度(PSMD)是一种新兴的基于弥散成像的标记,用于研究白质微观结构的早期微妙改变。我们评估了荷兰型遗传性 CAA(D-CAA)中 PSMD 的临床连续性及其与其他 CAA 相关 MRI 标记和认知症状的关联。我们纳入了有症状的D-CAA突变携带者,并根据弥散磁共振成像数据计算了PSMD。通过线性回归模型评估了 PSMD 水平、认知表现和 CAA 相关 MRI 标志物之间的关联。我们共纳入了 59 名参与者(25/34 为无症状/有症状;平均年龄为 39/58 岁)。有症状的 D-CAA 基因突变携带者(中位数 [范围] 4.90 [2.77-9.50]mm2/s × 10-4)与无症状的基因突变携带者(2.62 [1.96-3.43]mm2/s × 10-4)相比,PSMD 水平随着疾病严重程度的增加而升高。
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引用次数: 0
期刊
Journal of Cerebral Blood Flow and Metabolism
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